PROJECT SUMMARY/ABSTRACT The overall goal of this proposal is to determine the efficacy of resistance exercise training in preventing the decline in physical function in men with prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). As testosterone has a central role in the stimulation of prostate tissue, ADT is the cornerstone of treatment in men with high grade and metastatic PCa. ADT results in castrate levels of serum testosterone and this profound androgen deficiency leads to a reduction in lean mass and an increase in fat mass. These perturbations in body composition follow an aggressive course in these men as loss of lean mass is evident within 6-8 weeks of starting ADT. These unfavorable changes in body composition result in decreased muscle strength, which in turn, results in a decline in physical function. These adverse effects have serious consequences as men on ADT have a higher risk of frailty and falls compared with men with PCa who do not undergo ADT and are only treated with prostatectomy. Despite declines in these functional tasks that are patient-important and critical to maintenance of independence, not a single randomized trial has been performed in these men to evaluate the efficacy of a structured exercise regimen in preventing decline in physical function. A handful of previous studies had only enrolled men who were already receiving ADT and had already encountered significant muscle atrophy; therefore, as expected, no meaningful improvements in physical function were seen. Furthermore, previous studies did not provide equal attention to control groups. We propose a randomized, controlled, parallel group trial to determine the efficacy of 6-months of structured resistance exercise training in preventing the decline in physical function (assessed by loaded stair climbing power) in men age 60 years and older who are about to begin ADT for PCa. We will also provide equal attention to the control group using structured, patient-important, but outcome innocuous interventions (flexibility and balance exercises). We will also evaluate the efficacy of exercise training on muscle mass (DEXA scan), muscle strength (1RM method), QOL (SF-36 questionnaire) and fatigue (FACIT-F questionnaire). The findings of this trial will lay the groundwork for definitive intervention trials to prevent hard outcomes of frailty and falls in men undergoing ADT. As frailty imposes a significant public health burden and is associated with diminished functional capacity and resilience, the proposed trial is likely to have a substantial clinical impact in the overall health and independence of this patient population.